38 research outputs found
A Dominant Negative Inhibitor of the Egr Family of Transcription Regulatory Factors Suppresses Cerebellar Granule Cell Apoptosis by Blocking c-Jun Activation
No full textA Dominant Negative Egr Inhibitor Blocks Nerve Growth Factor-Induced Neurite Outgrowth by Suppressing c-Jun Activation: Role of an Egr/c-Jun Complex
No full textMembers of the Egr family of transcription factors are rapidly and robustly induced by neurotransmitters and neurotrophins and have been implicated in mediating enduring changes in neuronal function elicited by these stimuli. Because we have found in previous studies that a dominant negative inhibitor of Egr action, the Egr zinc finger domain (ZnEgr), blocks NGF-induced neurite outgrowth in PC12 cells, we have used this preparation to help identify the downstream targets of Egr proteins involved in plasticity. Our investigation into the mechanism of action of ZnEgr indicates that it blocks NGF-induced neurite outgrowth by suppressing activation of c-Jun, a critical step in the signaling pathway mediating this response. Although we had assumed that ZnEgr exerts its effects by binding to the Egr response element (ERE) and thereby blocking target gene regulation by Egr proteins, this classical mode of action appears to be too slow to mediate the effects of Egr proteins on c-Jun activation. In evaluating alternative ERE-independent mechanisms of Egr (and ZnEgr) action, we found that Egr1 and c-Jun coprecipitate and that ZnEgr disrupts formation of the Egr1/c-Jun complex. Furthermore, mutations of ZnEgr that greatly impair or abolish its ability to bind to the ERE do not block its ability to suppress c-Jun activation or neurite outgrowth induced by NGF. Accordingly, our studies indicate that Egr and ZnEgr proteins regulate c-Jun activation via a novel mechanism, protein–protein interaction with c-Jun, rather than via their classical mode of action, binding to the ERE.</jats:p
The effect of age on frontal lobe related cognitive functions of unmedicated depressed patients
No full textAssessment of negative symptoms and depression in schizophrenia: Revision of the SANS and how it relates to the PANSS and CDSS
No full textBlockade of NGF-Induced Neurite Outgrowth by a Dominant-Negative Inhibitor of the Egr Family of Transcription Regulatory Factors
No full textAlthough it is well established that members of the Egr family of transcription regulatory factors are induced in many neuronal plasticity paradigms, it is still unclear what role, if any, they play in this process. Because NGF stimulation of pheochromocytoma 12 cells elicits a robust induction of Egr family members, we have investigated their role in mediating long-term effects elicited by NGF in these cells by using the Egr zinc finger DNA-binding domain as a selective antagonist of Egr family-mediated transcription. We report that expression of this Egr inhibitor construct suppresses neurite outgrowth elicited by NGF but not by dibutyryl cAMP. To check that this Egr inhibitor construct does not act by blocking the MEK/ERK pathway, which is known to mediate NGF-induced neurite outgrowth, we confirmed that the Egr inhibitor construct does not block NGF activation of Elk1-mediated transcription, a response that is dependent on this pathway. Conversely, inhibition of MEK does not impair Egr family-mediated transcription. Thus, we conclude (1) that induction of Egr family members and activation of the MEK/ERK pathway by NGF are mediated by separate signaling pathways and (2) that both are required to trigger neurite outgrowth induced by NGF.</jats:p
Deep transcranial magnetic stimulation add-on for treatment of negative symptoms and cognitive deficits of schizophrenia: a feasibility study
No full textLong-term effects of transcranial magnetic stimulation on hippocampal reactivity to afferent stimulation
No full textTranscranial magnetic stimulation (TMS) has become a prom-ising treatment of affective disorders in humans, yet the neuro-nal basis of its long-lasting effects in the brain is still unknown. We studied acute and lasting effects of TMS on reactivity of the rat hippocampus to stimulation of the perforant path. Applica-tion of TMS to the brain of the anesthetized rat caused a dose-dependent transient increase in population spike (PS) response of the dentate gyrus to perforant path stimulation. In addition, TMS caused a marked decrease in inhibition and an increase in paired-pulse potentiation of reactivity to stimulation of the perforant path. Also, TMS suppressed the ability of fenfluramine (FFA), a serotonin releaser, to potentiate PS re-sponse to perforant path stimulation. Chronic TMS did not affect single population spikes but caused an increase in paired-pulse potentiation, which was still evident 3 weeks afte
The effects of oxytocin on fear recognition in patients with schizophrenia and in healthy controls
No full textIndividuals who suffer from schizophrenia often show a marked deficit in recognition of emotional facial expressions, as part of broader impairment of social cognition. Research has shown that recognition of negative emotions, specifically fear recognition, is particularly impaired among patients with schizophrenia. Recently we reported that intranasal administration of OT (IN OT) increased the ability to correctly recognize fear in a group of healthy men. The aim of the current study was to examine the effects of IN OT administration on fear recognition among patients with schizophrenia. Based on previous research, we also sought to examine a possible selective effect of OT dependent on baseline performance, hypothesizing that IN OT would have a greater enhancement effect on less proficient individuals. It was thus hypothesized that patients will show more improvement in fear recognition following the administration of IN OT as compared to controls. Sixty six participants (31 schizophrenia patients, 35 healthy controls) were enrolled in the current study. All participants received treatment of a single dose of 24 IU IN OT and an equivalent amount of placebo, one week apart. The participants’ ability to accurately recognize fear and happiness was evaluated using a face morphing task. Overall, as a group, both patients and healthy control participants were more accurate in recognizing fearful facial expressions, but not happy faces, following IN OT administration, as compared to their performance following placebo. IN OT did not differentially affect emotion recognition in patients and healthy controls. Yet, the results indicated a selective effect for IN OT, in which the hormone improves fear recognition only among individuals whose baseline performance was below the median, regardless of their psychiatric status
Group interpersonal psychotherapy for patients with major depression disorder – pilot study
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